scholarly journals Effects of gonadectomy and androgen on neuronal plasticity in motivation and reward related brain regions in the male rat

2020 ◽  
Author(s):  
Patty T. Huijgens ◽  
Eelke M.S. Snoeren ◽  
Robert L. Meisel ◽  
Paul G. Mermelstein

AbstractGonadal hormones affect neuronal morphology to ultimately regulate behavior. Here, we investigated the effect of both castration and androgen replacement on spine plasticity in the nucleus accumbens shell and core (NAcSh and NAcC), caudate putamen (CPu), medial amygdala (MeA), and medial preoptic nucleus (MPN). Intact and castrated (GDX) male rats were treated with dihydrotestosterone (DHT, 1.5mg) or vehicle (oil) in 3 experimental groups: intact-oil, GDX-oil and GDX-DHT. Spine density and morphology, measured 24 hours after injection, were determined through 3D reconstruction of DiI-labeled dendritic segments. GDX decreased spine density in the MPN, which was rescued by DHT treatment. MeA spine density increased in GDX-DHT animals compared to intact-oil animals. In the NAcSh, DHT decreased spine density, and also rapidly increased the number of pCREB+ cell bodies. These findings indicate that androgen signaling plays a role in the regulation of spine plasticity within neurocircuits involved in motivated behaviors.

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.


2000 ◽  
Vol 279 (2) ◽  
pp. H610-H618 ◽  
Author(s):  
Greg G. Geary ◽  
Diana N. Krause ◽  
Sue P. Duckles

Gender is known to influence the incidence and severity of cerebrovascular disease. In the present study, luminal diameter was measured in vitro in pressurized middle cerebral artery segments from male rats that were either untreated, orchiectomized (ORX), ORX with testosterone treatment (ORX+TEST), or ORX with estrogen treatment (ORX+EST). The maximal passive diameters (0 Ca2+ + 3 mM EDTA) of arteries from all four groups were similar. In endothelium-intact arteries, myogenic tone was significantly greater in arteries from untreated and ORX+TEST compared with arteries from either ORX or ORX+EST. During exposure to N G-nitro-l-arginine-methyl ester (l-NAME), an NO synthase (NOS) inhibitor, myogenic tone significantly increased in all groups. The effect of l-NAME was significantly greater in arteries from untreated and ORX+EST compared with arteries from ORX and ORX+TEST rats. Differences in myogenic tone between ORX and ORX+TEST persisted after inhibition of NOS. After endothelium removal or inhibition of the cyclooxygenase pathway combined with K+ channel blockers, myogenic tone differences between ORX and ORX+TEST were abolished. Wall thickness and forced dilation were not significantly different between arteries from ORX and ORX+TEST. Our data show that gonadal hormones affect myogenic tone in male rat cerebral arteries through NOS- and/or endothelium-dependent mechanisms.


2017 ◽  
Vol 233 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Marion Walser ◽  
Linus Schiöler ◽  
Jan Oscarsson ◽  
Maria A I Åberg ◽  
Ruth Wickelgren ◽  
...  

The endogenous secretion of growth hormone (GH) is sexually dimorphic in rats with females having a more even and males a more pulsatile secretion and low trough levels. The mode of GH administration, mimicking the sexually dimorphic secretion, has different systemic effects. In the brains of male rats, we have previously found that the mode of GH administration differently affects neuron–haemoglobin beta (Hbb) expression whereas effects on other transcripts were moderate. The different modes of GH administration could have different effects on brain transcripts in female rats. Hypophysectomised female rats were given GH either as injections twice daily or as continuous infusion and GH-responsive transcripts were assessed by quantitative reverse transcription polymerase chain reaction in the hippocampus and parietal cortex (cortex). The different modes of GH-administration markedly increased Hbb and 5′-aminolevulinate synthase 2 (Alas2) in both brain regions. As other effects were relatively moderate, a mixed model analysis (MMA) was used to investigate general effects of the treatments. In the hippocampus, MMA showed that GH-infusion suppressed glia- and neuron-related transcript expression levels, whereas GH-injections increased expression levels. In the cortex, GH-infusion instead increased neuron-related transcripts, whereas GH-injections had no significant effect. Interestingly, this contrasts to previous results obtained from male rat cortex where GH-infusion generally decreased expression levels. In conclusion, the results indicate that there is a small but significant difference in response to mode of GH administration in the hippocampus as compared to the cortex. For both modes of GH administration, there was a robust effect on Hbb and Alas2.


Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1357-1362 ◽  
Author(s):  
Luis F. Jacome ◽  
Ketti Barateli ◽  
Dina Buitrago ◽  
Franklin Lema ◽  
Maya Frankfurt ◽  
...  

Abstract 17β-estradiol (E2) rapidly, within minutes, activates behaviors and cognition by binding to membrane estrogen receptors, activating cell signaling cascades and increasing dendritic spines. In female rodents, E2 enhances spatial memory within 2–4 hours, and spine density is increased in the CA1 area of the hippocampus within 30–60 minutes. Although chronic gonadal hormone treatments in male rats alter cognition and spines/spine synapses and acute hormone effects occur in hippocampal slices, effects of acute, in vivo hormone administration in males are unknown. Therefore, we assessed rapid effects of E2 (20 μg/kg) and testosterone (T) (750 μg/kg) on spatial memory using the object placement task and on hippocampal spine density using Golgi impregnation. Orchidectomized rats received hormones immediately after the training trial and were tested for retention 2 hours later. Vehicle-injected orchidectomized males spent equal time exploring objects in the old and new locations, but E2- or T-treated subjects spent more time exploring objects at the new location, suggesting enhanced memory. Both hormones also increased spine density in CA1, but not the dentate gyrus, by 20%–40% at 30 minutes and 2 hours after injections. This report is the first, to our knowledge, to show E2 and T enhancements of memory and spine density within such a short time frame in male rats.


1981 ◽  
Vol 88 (3) ◽  
pp. 351-358 ◽  
Author(s):  
E. O. ALVAREZ ◽  
A. O. DONOSO

The levels of prolactin in the plasma of conscious male rats were determined at various times after an acute administration of histamine or a histamine releasing agent, compound 48/80, in three brain regions. The brain structures that were examined were, the caudal part of the preoptic area and anterior part of the anterior hypothalamic area (POA–AHA), the arcuate nucleus–ventromedial nucleus region (ARC–VMN) and the medial–basal amygdaloid nucleus of the limbic system (AME). A marked increase in plasma levels of prolactin was observed when implants of histamine were in the POA–AHA region. A more consistent increase was found when 1 μg histamine was injected in the same region; values of prolactin were about 3·6 times greater than in their controls injected with 0·9% saline. Such increased hormone levels lasted up to 2 h. A similar rise in prolactin level was found when the implants of histamine were located in the ARC–VMN region. When compound 48/80 or empty cannulae were placed in those brain regions that were examined, no changes in plasma levels of prolactin were induced. Both histamine and compound 48/80 elicited a delayed and long-lasting decrease of the high plasma level of prolactin present in rats bearing cannulae in the AME region. The results suggest that in the male rat, histaminergic sites, located in rostral and mediobasal hypothalamus and in the central area of the amygdala, are involved in the mechanisms controlling prolactin secretion.


2021 ◽  
Author(s):  
Ashley Bernardo ◽  
Philippe Lee ◽  
Michael Marcotte ◽  
Yeunus Mian ◽  
Zubair A. Khan ◽  
...  

AbstractChronic stress is a major risk factor for developing depressive disorders and animal models of stress recapitulate behavioral, cellular and molecular changes that are observed in human depression. Individuals exposed to chronic stress, or patients with MDD experience mood and cognitive dysfunctions. This is in part due to neuronal shrinkage in brain regions involved in several cognitive functions such as the prefrontal cortex (PFC) and the hippocampus (HPC). Also in the context of depression and chronic stress, expression levels and function of the main inhibitory neurotransmitter GABA are reduced. Thus far, drugs targeting this GABA deficit have failed to produce beneficial effects due to broad activity at various GABA receptor subunits, including the α1-subunit, resulting in broad side effects. However, refined and selective activity at the α2/3/5-subunit is hypothesized to exert beneficial effect, devoid of side effects.Here, we show that GL-II-73 and GL-I-54 exert positive allosteric modulation at the α5, and α2/3/5-contianing GABAA receptors respectively, and that they are effective both independently and in combination. Using unpredictable chronic mild stress (UCMS) experiments in male and female C57BL/6 mice (n=12 per group), we showed that acute and chronic administration of a GL-II-73/GL-I-54 racemic mixture (termed “GL-RM”) reduced anxiety-like phenotypes and reversed a working memory deficit in UCMS exposed mice. Brains from animals receiving chronic treatment were collected and stained using a Golgi staining technique. Using stereological approaches, neuronal morphology was reconstructed and dendritic length, spine count and spine density were assessed in pyramidal neurons of the PFC and hippocampus. Chronic GL-RM rescued spine density depletions caused by UCMS at apical and basal dendrites (PFC and CA1). Interestingly, spine densities in both brain regions were correlated to cognitive performance, confirming ameliorative benefits of GL-RM.Together, results support the value of selectively targeting GABAA receptors, excluding the α1-subunit, to overcome chronic stress-induced mood symptoms and cognitive deficits, as well as detriments in neuronal morphology. This study confirm results that were observed in old mice, using a α5-selective positive allosteric modulator, and reinforce the concept that the α2/3/5-containing GABAA receptor are suitable targets for the treatment of stress-induced disorders.


2015 ◽  
Vol 282 (1808) ◽  
pp. 20150042 ◽  
Author(s):  
Donna Tan ◽  
Linda Jing Ting Soh ◽  
Lee Wei Lim ◽  
Tan Chia Wei Daniel ◽  
Xiaodong Zhang ◽  
...  

Rats infected with the protozoan parasite Toxoplasma gondii exhibit reduced avoidance of predator odours. This behavioural change is likely to increase transmission of the parasite from rats to cats. Here, we show that infection with T. gondii increases the propensity of the infected rats to make more impulsive choices, manifested as delay aversion in an intertemporal choice task. Concomitantly, T. gondii infection causes reduction in dopamine content and neuronal spine density of the nucleus accumbens core, but not of the nucleus accumbens shell. These results are consistent with a role of the nucleus accumbens dopaminergic system in mediation of choice impulsivity and goal-directed behaviours. Our observations suggest that T. gondii infection in rats causes a syndromic shift in related behavioural constructs of innate aversion and making foraging decisions.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 424
Author(s):  
Radoslaw Piotr Radzki ◽  
Marek Bienko ◽  
Dariusz Wolski ◽  
Monika Ostapiuk ◽  
Pawel Polak ◽  
...  

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A45-A45
Author(s):  
Irma Gvilia ◽  
Sunil Kumar ◽  
Dennis McGinty ◽  
Ronald Szymusiak

Abstract Introduction We have previously shown that pharmacological elevation of corticotropin releasing factor (CRF) signaling in the brain results in exacerbation of sleep disturbances evoked by the exposure of rats to an acute stressor, the dirty cage of a male rat. In the present study we (1) assessed wake-sleep behavior of mice after the exposure to the dirty cage stress paradigm, and (2) examined the effect of chemogenetic silencing of CRF neurons in the hypothalamic paraventricular nucleus (PVN) on sleep occurring following the exposure to this stressor. Methods First, a group of mice (n=12) was implanted with EEG/EMG electrodes. In two weeks, post-surgery, six mice were transferred to dirty cages of male rats and recorded for 24 hours. Control mice were transferred to clean cages. In the second study, a group of CRF-ires-cre mice (n=8) received bilateral injections of AAV-hSyn-DIO-hM4Di-mCherry targeting the PVN. The other group of CRF-ires-cre mice (n=8) was injected AAV-hSyn-DIO-mCherry (control vector). All mice were implanted with EEG/EMG electrodes. Dirty cage experiments were started following a 4-week postsurgical period to allow gene recombination and expression. Mice were subjected to intraperitoneal (IP) administration of clozapine-n-oxide (CNO; 3 mg/kg) at ZT1, placed into dirty cages, and recorded for post-stress sleep. Results: Results In mice expressing hM4Di inhibitory DREADDs (designer receptors activated by designer drugs) versus mice injected with control AAV, IP CNO (3 mg/kg) resulted in a significant decrease of post-stress sleep onset latency, decrease of time spent in wakefulness (first hour, 74±5.3 vs. 89±11.0, second hour, 37.2±10.3% vs. 81.3±9.3%; third hour, 40.1±3.3% vs. 47.1±14.3%; fourth hour, 44.4±6.0 vs. 55.5±9.9), and increase in non-rapid eye movement (NREM) sleep time (26.0±5.4% vs. 11.0±11.1%; 62.8%±9.8 vs. 18.7 ± 9.6%; 59.9±3.2% vs. 52.9±14.5%; 55.6±6.2 vs. 44.5±10.0). The hM4Di expressing mice exhibited longer episodes of NREM sleep, compared to mice injected with control AAV (first hour, 133.3±80.1sec vs. 21±1.7sec; second hour, 43256±83.4sec vs. 73.5±44.1sec; third hour, 459.2±139.8sec vs. 139±80.6sec; fourth hour, 233.1±82.6sec vs. 190±72.3sec). Conclusion Chemogenetic silencing of CRF neurons in the PVN attenuates acute stress-induced sleep disturbance in mice. Support (if any) Supported by Department of Veterans Affairs Merit Review Grant # BX00155605 and SRNSF (Georgia) grant FR-18-12533


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Peng Chen ◽  
Hongyang Jing ◽  
Mingtao Xiong ◽  
Qian Zhang ◽  
Dong Lin ◽  
...  

AbstractThe genes encoding for neuregulin1 (NRG1), a growth factor, and its receptor ErbB4 are both risk factors of major depression disorder and schizophrenia (SZ). They have been implicated in neural development and synaptic plasticity. However, exactly how NRG1 variations lead to SZ remains unclear. Indeed, NRG1 levels are increased in postmortem brain tissues of patients with brain disorders. Here, we studied the effects of high-level NRG1 on dendritic spine development and function. We showed that spine density in the prefrontal cortex and hippocampus was reduced in mice (ctoNrg1) that overexpressed NRG1 in neurons. The frequency of miniature excitatory postsynaptic currents (mEPSCs) was reduced in both brain regions of ctoNrg1 mice. High expression of NRG1 activated LIMK1 and increased cofilin phosphorylation in postsynaptic densities. Spine reduction was attenuated by inhibiting LIMK1 or blocking the NRG1–LIMK1 interaction, or by restoring NRG1 protein level. These results indicate that a normal NRG1 protein level is necessary for spine homeostasis and suggest a pathophysiological mechanism of abnormal spines in relevant brain disorders.


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